Positive results of a phase 2 assessment of oral tavapadon, previously known as PF-06649751, in patients with early-stage Parkinson disease, have been announced by Cerevel Therapeutics. The investigational agent met its primary end point by showing a statistically significant improvement in motor symptoms after 15 weeks.1
The data ultimately showed a change of –9.0 points in Unified Parkinson's Disease Rating Scale (UPDRS) Part III scores for those treated with tavapadon, compared to –4.3 for those administered placebo (least-squares mean, –4.8; P =.0407). Additionally, treatment compliance was high in both groups and 82% of patients who received tavapadon completed the trial.
The results were presented by David Gray, PhD, vice president of chemistry, Cerevel Therapeutics, and study team leader, at the 2019 International Congress of Parkinson’s Disease and Movement Disorders, in Nice, France.
“Current approaches and treatment options for patients with Parkinson disease are often associated with significant complications, troublesome side effects or limited efficacy,” Gray said in a statement. “I’m encouraged by these results, which demonstrated that tavapadon was significantly more effective than placebo in improving motor symptoms and was well tolerated. It has the potential to be a promising new treatment option for people with Parkinson’s disease.”
The randomized, flexible-dose study included 57 patients aged 45 to 80 years with Parkinson and a disease severity ranging from Hoehn & Yahr stage 1 to 3. The study included a 9-week dose optimization period followed by a 6-week period of stable dosing. In phase 1 study, tavapadon doses were 0.75 mg, 1.5 mg, 3 mg, 6 mg, and 9 mg, including an open-label multiple ascending dose study, which gave once-daily doses with up-titration to 5 mg, 15 mg, and 25 mg.2
The Patient Global Impression of Change (PGI-C) and Epworth Sleepiness Scale (ESS) were secondary end points.
After 15 weeks, 50% of those treated with the study agent reported PCI-C statuses of either much improved or very much improved. In comparison, the placebo group experienced this at in 25% of patients. As for ESS, no effects of significance were reported by either placebo or the highly selective dopamine D1/D5 agonist at weeks 9 or 15.
“The positive Phase 2 efficacy and safety data presented today reinforce the potential of tavapadon as a new treatment option for patients with Parkinson’s disease,” Raymond Sanchez, MD, chief medical officer, Cerevel Therapeutics, said in a statement. “Given the favorable profile of tavapadon in clinical studies to date, we see potential for this novel therapy in a variety of treatment settings for Parkinson’s disease, both as a monotherapy for patients with early-stage disease and as an adjunct to levodopa for patients with late-stage disease.”
The Cerevel agent also showed a favorable tolerability and safety profile. Most of the adverse events (AEs) were deemed mild or moderate, with the most common being were nausea, headache, dry mouth, somnolence, and tremor.
“Over the course of 2020, we plan to initiate a robust phase 3 development program to fully characterize the utility of tavapadon in patients with early- and late-stage Parkinson,” Sanchez said.
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1. Cerevel Therapeutics Announces Positive Results from a Phase 2 Study of Tavapadon in Patients with Early-stage Parkinson’s Disease [press release]. Boston, MA: Cerevel Therapeutics; Published September 23, 2019. businesswire.com/news/home/20190923005097/en/Cerevel-Therapeutics-Announces-Positive-Results-Phase-2. Accessed September 23, 2019.
2. Sohur US, Gray DL, Duvvuri S, Zhang Y, Thayer K, Feng G. Phase 1 Parkinson's Disease Studies Show the Dopamine D1/D5 Agonist PF-06649751 is Safe and Well Tolerated. Neurol Ther. 2018;7(2):307-319. doi: 10.1007/s40120-018-0114-z.